Huntington's Disease: Genetics, Symptoms, and Hope for the Future
Huntington's disease (HD) is one of those rare conditions that affects not just the patient but the entire family—medically, emotionally and genetically. This inherited brain disorder causes gradual breakdown of nerve cells especially in the parts of the brain involved in movement, thinking and mood regulation. Although rare, affecting 3 to 7 people per 100,000 globally, its impact is profound and relentless. With no cure in sight, HD is at the center of intense research to understand its molecular roots and develop targeted therapies [1].
Huntington's disease is inherited in an autosomal dominant pattern, meaning if a person inherits one copy of the defective gene they will develop the disease. The culprit is a genetic mutation in the hd gene (also known as the huntingtin gene), where a DNA segment—specifically a CAG trinucleotide repeat—is abnormally expanded. Normally this segment is repeated 10 to 35 times. In HD it's repeated 36 times or more, sometimes even in the 100s [3] [4] [5] [6]. Huntington's disease is caused by a genetic mutation in the huntingtin gene, specifically the HD mutation involving expanded CAG repeats.
This expanded repeat leads to the creation of a toxic version of a protein called huntingtin which misfolds and accumulates in brain cells. Over time these protein clumps disrupt cellular function and lead to death of neurons—especially in the striatum and cortex, areas responsible for motor control and cognition [4] [5]. The loss of nerve cells in these regions is what causes the symptoms of Huntington's disease. Different genetic variants can influence the age of onset and progression of the disease.
Researchers have identified two distinct disease phases: an early phase where the brain seems to compensate for the damage and a later phase where symptoms are more visible and rapid neurodegeneration [7]. Understanding the disease process at the molecular level is key to developing new treatments.
Huntington's disease symptoms usually emerge between 30-50 years and progress over 15-20 years. The classic triad of symptoms includes:
The range of disease symptoms includes symptoms of HD and symptoms of Huntington's disease, covering motor, cognitive and behavioral changes throughout the course of the illness.
Research in 2025 has shown that changes in how the striatum connects with the hippocampus may explain some of the memory difficulties HD patients experience, especially those involving spatial awareness [10]. Also worth noting are lesser-known symptoms like loss of smell in advanced disease stages [11] and subtle sex-based differences in disease expression. For example, male patients may have lower levels of 17β-estradiol and reduced number of DARPP-32+ neurons, which may influence disease severity [12]. Other symptoms like sleep disturbances and weight loss may also appear as the disease advances.
As the disease progresses symptoms worsen over time with increasing severity of movement disorders, cognitive decline and behavioral changes.
Motor symptoms especially uncontrolled movements and balance problems can lead to physical injury from falls or accidents, further impacting quality of life.
Juvenile Huntington's disease is a rare form that affects children and adolescents, often presenting with unique features like seizures and more rapid progression compared to adult-onset cases.
Huntington's disease diagnosis is confirmed by a genetic test showing 36 or more CAG repeats in the HTT gene. However, the diagnostic process also involves:
Presymptomatic genetic testing is available for individuals without known family history of HD. While this can provide clarity, it raises ethical challenges, especially around mental health support and family planning [9].
Beyond the faulty gene itself, scientists have found a cascade of biological disruptions that drive HD. Imaging studies show that HD affects brain structure and function, leading to progressive changes in key brain regions and chemical systems:
Huntington's disease affects both physical and mental health, leading to movement disorders, cognitive decline and psychiatric symptoms that worsen over time.
Each of these changes leads to neuronal death, providing multiple targets for therapeutic intervention. Individuals who inherit the genetic mutation will develop Huntington's disease.
There's no cure for HD yet, but several treatments can help manage symptoms:
More exciting, however, are the experimental approaches in development:
For updates on these trials, you can follow progress via resources like HDSA.org, the ClinicalTrials.gov HD portal, or the European Huntington's Disease Network.
People with Huntington's disease benefit from tailored care and support, and their involvement in research and clinical trials is crucial for developing better therapies.
Living with Huntington's isn't just about managing symptoms—it's about navigating a complex emotional and social landscape. Many patients grapple with:
Family members are often deeply involved in caregiving, emotional support, and making important decisions throughout the course of the disease.
Because of this, a team-based approach to care is critical. Neurologists, psychiatrists, genetic counselors, social workers, therapists, and genetic counseling services all play a part in supporting HD patients and their loved ones. A genetic counselor is a healthcare professional who guides patients through the genetic testing process, explains inheritance patterns, and answers questions about the benefits and risks of testing.
Huntington's disease is a devastating diagnosis, but the landscape is slowly shifting. Thanks to advances in genetic research, brain imaging, and experimental therapies, we're moving closer to more personalized and effective treatments. Until then, early diagnosis, supportive care, and active participation in research remain key to improving quality of life for those affected by HD.
[1] Stoker, T. B., Mason, S. L., Greenland, J. C., Holden, S. T., Santini, H., & Barker, R. A. (2022). Huntington's disease: diagnosis and management. Practical neurology, 22(1), 32–41. https://doi.org/10.1136/practneurol-2021-003074
[2] Walker F. O. (2007). Huntington's disease. Lancet (London, England), 369(9557), 218–228. https://doi.org/10.1016/S0140-6736(07)60111-1
[3] Kim, A., Lalonde, K., Truesdell, A., Gomes Welter, P., Brocardo, P. S., Rosenstock, T. R., & Gil-Mohapel, J. (2021). New Avenues for the Treatment of Huntington's Disease. International journal of molecular sciences, 22(16), 8363. https://doi.org/10.3390/ijms22168363
[4] Ghosh, R., & Tabrizi, S. J. (2018). Huntington disease. Handbook of clinical neurology, 147, 255–278. https://doi.org/10.1016/B978-0-444-63233-3.00017-8
[5] McColgan, P., & Tabrizi, S. J. (2018). Huntington's disease: a clinical review. European journal of neurology, 25(1), 24–34. https://doi.org/10.1111/ene.13413
[6] Bates, G. P., Dorsey, R., Gusella, J. F., Hayden, M. R., Kay, C., Leavitt, B. R., Nance, M., Ross, C. A., Scahill, R. I., Wetzel, R., Wild, E. J., & Tabrizi, S. J. (2015). Huntington disease. Nature reviews. Disease primers, 1, 15005. https://doi.org/10.1038/nrdp.2015.5
[7] Hong, E. P., MacDonald, M. E., Wheeler, V. C., Jones, L., Holmans, P., Orth, M., Monckton, D. G., Long, J. D., Kwak, S., Gusella, J. F., & Lee, J. M. (2021). Huntington's Disease Pathogenesis: Two Sequential Components. Journal of Huntington's disease, 10(1), 35–51. https://doi.org/10.3233/JHD-200427
[8] Wolf, B., Schwarzer, A., Côté, A. L., Hampton, T. H., Schwaab, T., Huarte, E., Tomlinson, C. R., Gui, J., Fisher, J. L., Fadul, C. E., Hamilton, J. W., & Ernstoff, M. S. (2012). Gene expression profile of peripheral blood lymphocytes from renal cell carcinoma patients treated with IL-2, interferon-α and dendritic cell vaccine. PloS one, 7(12), e50221. https://doi.org/10.1371/journal.pone.0050221
[9] Rodríguez-Arribas, M., Yakhine-Diop, S. M. S., Pedro, J. M. B., Gómez-Suaga, P., Gómez-Sánchez, R., Martínez-Chacón, G., Fuentes, J. M., González-Polo, R. A., & Niso-Santano, M. (2017). Mitochondria-Associated Membranes (MAMs): Overview and Its Role in Parkinson's Disease. Molecular neurobiology, 54(8), 6287–6303. https://doi.org/10.1007/s12035-016-0140-8
[10] Glikmann-Johnston, Y., Delagneau, G., Barta, T., Stout, J. C., & Razi, A. (2025). Neural Mechanisms of Object Location Memory in Huntington's Disease. Movement disorders : official journal of the Movement Disorder Society, 10.1002/mds.30232. Advance online publication. https://doi.org/10.1002/mds.30232
[11] Bylsma, F. W., Moberg, P. J., Doty, R. L., & Brandt, J. (1997). Odor identification in Huntington's disease patients and asymptomatic gene carriers. The Journal of neuropsychiatry and clinical neurosciences, 9(4), 598–600. https://doi.org/10.1176/jnp.9.4.598
[12] Bode, F. J., Stephan, M., Suhling, H., Pabst, R., Straub, R. H., Raber, K. A., Bonin, M., Nguyen, H. P., Riess, O., Bauer, A., Sjoberg, C., Petersén, A., & von Hörsten, S. (2008). Sex differences in a transgenic rat model of Huntington's disease: decreased 17beta-estradiol levels correlate with reduced numbers of DARPP32+ neurons in males. Human molecular genetics, 17(17), 2595–2609. https://doi.org/10.1093/hmg/ddn159
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Los Angeles Times
3 days ago
- Los Angeles Times
Huntington's Disease: Genetics, Symptoms, and Hope for the Future
Huntington's disease (HD) is one of those rare conditions that affects not just the patient but the entire family—medically, emotionally and genetically. This inherited brain disorder causes gradual breakdown of nerve cells especially in the parts of the brain involved in movement, thinking and mood regulation. Although rare, affecting 3 to 7 people per 100,000 globally, its impact is profound and relentless. With no cure in sight, HD is at the center of intense research to understand its molecular roots and develop targeted therapies [1]. Huntington's disease is inherited in an autosomal dominant pattern, meaning if a person inherits one copy of the defective gene they will develop the disease. The culprit is a genetic mutation in the hd gene (also known as the huntingtin gene), where a DNA segment—specifically a CAG trinucleotide repeat—is abnormally expanded. Normally this segment is repeated 10 to 35 times. In HD it's repeated 36 times or more, sometimes even in the 100s [3] [4] [5] [6]. Huntington's disease is caused by a genetic mutation in the huntingtin gene, specifically the HD mutation involving expanded CAG repeats. This expanded repeat leads to the creation of a toxic version of a protein called huntingtin which misfolds and accumulates in brain cells. Over time these protein clumps disrupt cellular function and lead to death of neurons—especially in the striatum and cortex, areas responsible for motor control and cognition [4] [5]. The loss of nerve cells in these regions is what causes the symptoms of Huntington's disease. Different genetic variants can influence the age of onset and progression of the disease. Researchers have identified two distinct disease phases: an early phase where the brain seems to compensate for the damage and a later phase where symptoms are more visible and rapid neurodegeneration [7]. Understanding the disease process at the molecular level is key to developing new treatments. Huntington's disease symptoms usually emerge between 30-50 years and progress over 15-20 years. The classic triad of symptoms includes: The range of disease symptoms includes symptoms of HD and symptoms of Huntington's disease, covering motor, cognitive and behavioral changes throughout the course of the illness. Research in 2025 has shown that changes in how the striatum connects with the hippocampus may explain some of the memory difficulties HD patients experience, especially those involving spatial awareness [10]. Also worth noting are lesser-known symptoms like loss of smell in advanced disease stages [11] and subtle sex-based differences in disease expression. For example, male patients may have lower levels of 17β-estradiol and reduced number of DARPP-32+ neurons, which may influence disease severity [12]. Other symptoms like sleep disturbances and weight loss may also appear as the disease advances. As the disease progresses symptoms worsen over time with increasing severity of movement disorders, cognitive decline and behavioral changes. Motor symptoms especially uncontrolled movements and balance problems can lead to physical injury from falls or accidents, further impacting quality of life. Juvenile Huntington's disease is a rare form that affects children and adolescents, often presenting with unique features like seizures and more rapid progression compared to adult-onset cases. Huntington's disease diagnosis is confirmed by a genetic test showing 36 or more CAG repeats in the HTT gene. However, the diagnostic process also involves: Presymptomatic genetic testing is available for individuals without known family history of HD. While this can provide clarity, it raises ethical challenges, especially around mental health support and family planning [9]. Beyond the faulty gene itself, scientists have found a cascade of biological disruptions that drive HD. Imaging studies show that HD affects brain structure and function, leading to progressive changes in key brain regions and chemical systems: Huntington's disease affects both physical and mental health, leading to movement disorders, cognitive decline and psychiatric symptoms that worsen over time. Each of these changes leads to neuronal death, providing multiple targets for therapeutic intervention. Individuals who inherit the genetic mutation will develop Huntington's disease. There's no cure for HD yet, but several treatments can help manage symptoms: More exciting, however, are the experimental approaches in development: For updates on these trials, you can follow progress via resources like the HD portal, or the European Huntington's Disease Network. People with Huntington's disease benefit from tailored care and support, and their involvement in research and clinical trials is crucial for developing better therapies. Living with Huntington's isn't just about managing symptoms—it's about navigating a complex emotional and social landscape. Many patients grapple with: Family members are often deeply involved in caregiving, emotional support, and making important decisions throughout the course of the disease. Because of this, a team-based approach to care is critical. Neurologists, psychiatrists, genetic counselors, social workers, therapists, and genetic counseling services all play a part in supporting HD patients and their loved ones. A genetic counselor is a healthcare professional who guides patients through the genetic testing process, explains inheritance patterns, and answers questions about the benefits and risks of testing. Huntington's disease is a devastating diagnosis, but the landscape is slowly shifting. Thanks to advances in genetic research, brain imaging, and experimental therapies, we're moving closer to more personalized and effective treatments. Until then, early diagnosis, supportive care, and active participation in research remain key to improving quality of life for those affected by HD. [1] Stoker, T. B., Mason, S. L., Greenland, J. C., Holden, S. T., Santini, H., & Barker, R. A. (2022). Huntington's disease: diagnosis and management. Practical neurology, 22(1), 32–41. [2] Walker F. O. (2007). Huntington's disease. Lancet (London, England), 369(9557), 218–228. [3] Kim, A., Lalonde, K., Truesdell, A., Gomes Welter, P., Brocardo, P. S., Rosenstock, T. R., & Gil-Mohapel, J. (2021). New Avenues for the Treatment of Huntington's Disease. International journal of molecular sciences, 22(16), 8363. [4] Ghosh, R., & Tabrizi, S. J. (2018). Huntington disease. Handbook of clinical neurology, 147, 255–278. [5] McColgan, P., & Tabrizi, S. J. (2018). Huntington's disease: a clinical review. European journal of neurology, 25(1), 24–34. [6] Bates, G. P., Dorsey, R., Gusella, J. F., Hayden, M. R., Kay, C., Leavitt, B. R., Nance, M., Ross, C. A., Scahill, R. I., Wetzel, R., Wild, E. J., & Tabrizi, S. J. (2015). Huntington disease. Nature reviews. Disease primers, 1, 15005. [7] Hong, E. P., MacDonald, M. E., Wheeler, V. C., Jones, L., Holmans, P., Orth, M., Monckton, D. G., Long, J. D., Kwak, S., Gusella, J. F., & Lee, J. M. (2021). Huntington's Disease Pathogenesis: Two Sequential Components. Journal of Huntington's disease, 10(1), 35–51. [8] Wolf, B., Schwarzer, A., Côté, A. L., Hampton, T. H., Schwaab, T., Huarte, E., Tomlinson, C. R., Gui, J., Fisher, J. L., Fadul, C. E., Hamilton, J. W., & Ernstoff, M. S. (2012). Gene expression profile of peripheral blood lymphocytes from renal cell carcinoma patients treated with IL-2, interferon-α and dendritic cell vaccine. PloS one, 7(12), e50221. [9] Rodríguez-Arribas, M., Yakhine-Diop, S. M. S., Pedro, J. M. B., Gómez-Suaga, P., Gómez-Sánchez, R., Martínez-Chacón, G., Fuentes, J. M., González-Polo, R. A., & Niso-Santano, M. (2017). Mitochondria-Associated Membranes (MAMs): Overview and Its Role in Parkinson's Disease. Molecular neurobiology, 54(8), 6287–6303. [10] Glikmann-Johnston, Y., Delagneau, G., Barta, T., Stout, J. C., & Razi, A. (2025). Neural Mechanisms of Object Location Memory in Huntington's Disease. Movement disorders : official journal of the Movement Disorder Society, 10.1002/mds.30232. Advance online publication. [11] Bylsma, F. W., Moberg, P. J., Doty, R. L., & Brandt, J. (1997). Odor identification in Huntington's disease patients and asymptomatic gene carriers. The Journal of neuropsychiatry and clinical neurosciences, 9(4), 598–600. [12] Bode, F. J., Stephan, M., Suhling, H., Pabst, R., Straub, R. H., Raber, K. A., Bonin, M., Nguyen, H. P., Riess, O., Bauer, A., Sjoberg, C., Petersén, A., & von Hörsten, S. (2008). Sex differences in a transgenic rat model of Huntington's disease: decreased 17beta-estradiol levels correlate with reduced numbers of DARPP32+ neurons in males. Human molecular genetics, 17(17), 2595–2609.
Yahoo
3 days ago
- Yahoo
Skyhawk Therapeutics Announces First Patient Dosed in Phase 2/3 FALCON-HD Trial of SKY-0515 for Huntington's Disease
SKY-0515 is an oral small molecule designed to reduce the production of both huntingtin (HTT) and PMS1 proteins—two key drivers of HD pathology Initiation of the FALCON-HD trial follows promising Phase 1 results demonstrating up to 72% reduction in HTT mRNA in healthy volunteers The SKY-0515 Phase 1 trial in patients with Huntington's disease reached full enrollment ahead of schedule BOSTON, June 18, 2025 /PRNewswire/ -- Skyhawk Therapeutics, Inc., a clinical-stage biotechnology company developing novel small molecule therapies designed to modulate critical RNA targets, today announced that the first patient has been dosed in its Phase 2/3 FALCON-HD trial evaluating SKY-0515, an investigational oral RNA splicing modulator for the treatment of Huntington's disease (HD). SKY-0515 is designed to reduce the production of both HTT and PMS1 proteins—two key drivers of HD pathology. In a Phase 1 study in healthy volunteers, SKY-0515 demonstrated dose-dependent HTT mRNA reduction, achieving an average of 72% lowering at the highest dose tested. The compound was generally well tolerated across all doses. Additionally, the Company's Phase 1 trial in HD patients, which began in January 2025, completed enrollment ahead of schedule in March 2025. "Dosing the first patient in our FALCON-HD trial marks a significant milestone in our mission to develop a disease-modifying therapy for Huntington's patients," said Bill Haney, Founder and Chief Executive Officer of Skyhawk Therapeutics. "Building on our compelling Phase 1 data, we are eager to assess SKY-0515's potential to make a meaningful difference in the lives of patients affected by this devastating condition." FALCON-HD is a Phase 2/3 randomized, double-blind, placebo-controlled, dose ranging study to evaluate the pharmacodynamics, safety, and efficacy of SKY-0515 in participants with Stage 2 and early Stage 3 HD. The trial includes multiple sites across Australia and New Zealand. The initial dosing took place at Flinders Medical Centre in Adelaide, Australia. "We are pleased to participate in this important clinical trial and to have dosed the first patient here at Flinders," said Dr. Karyn Boundy, FRACP, Neurologist, Principal Investigator at Flinders Medical Centre. "Given the lack of approved disease-modifying treatments for Huntington's disease, we are hopeful that SKY-0515 could offer a new therapeutic option for patients." "As Skyhawk kicks off their Phase 2/3 FALCON-HD trial in Australia and New Zealand, the international Huntington's community looks forward to expansion worldwide," said Ed Wild, professor of neurology at the University College London. "SKY-0515's unique ability to reduce both HTT and PMS1 could meaningfully enhance therapeutic impact beyond that of lowering HTT alone." About the FALCON-HD TrialFALCON-HD (NCT06873334) is a Phase 2/3 randomized, double-blind, placebo-controlled, dose ranging study to evaluate the pharmacodynamics, safety, and efficacy of SKY-0515 in participants with Stage 2 and early Stage 3 HD. The trial plans to enroll 120 subjects across 10 sites in Australia and New Zealand. Eligible patients will receive a once-daily oral dose of SKY-0515 at one of three dose levels, or placebo, for a treatment period of at least 12 months. The trial aims to assess the potential of SKY-0515 to modulate RNA splicing and reduce the production of huntingtin (HTT) and PMS1 proteins, which are implicated in the pathology of Huntington's disease. Additional information about FALCON-HD, including participating sites and eligibility criteria, can be found at and About SKY-0515SKY-0515 is an orally administered small molecule RNA splicing modulator developed through Skyhawk's proprietary platform. It is designed to reduce production of both huntingtin (HTT) and PMS1 proteins, two key contributors to Huntington's disease. SKY-0515 has shown robust, dose-dependent HTT mRNA reduction—up to 72%—in healthy volunteer studies, with favorable safety and tolerability. SKY-0515 is currently being evaluated in a Phase 2/3 clinical trial. About Skyhawk TherapeuticsSkyhawk Therapeutics is a clinical-stage biotechnology company focused on the discovery and development of novel small molecule therapies designed to modulate critical RNA targets and revolutionize patient treatment for some of the world's most intractable diseases. Skyhawk's discovery expertise is rooted in its proprietary drug discovery platform, which assesses, identifies, and tests RNA splicing targets and small molecules across a broad range of therapeutic areas and disease states. Skyhawk has built collaborations with multiple pharma partners that leverage Skyhawk's novel platform across disease areas including neurodegenerative disease, autoimmune disease, and oncology. For more information visit Skyhawk ContactsKyle Dow, VP Corporate Logo - View original content: SOURCE Skyhawk Therapeutics Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Yahoo
11-06-2025
- Yahoo
uniQure Announces Appointment of Kylie O'Keefe as Chief Customer and Strategy Officer
~ Proven biotech executive to lead commercialization of AMT-130 in Huntington's disease ~ LEXINGTON, Mass. and AMSTERDAM, June 11, 2025 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced the appointment of Kylie O'Keefe as Chief Customer and Strategy Officer, effective June 6, 2025. In this role, Ms. O'Keefe will lead the development and execution of uniQure's global commercialization strategy for AMT-130, the Company's investigational gene therapy for the treatment of Huntington's disease. Her responsibilities include all commercial functions and medical affairs. Ms. O'Keefe was most recently Chief Commercial Officer at PTC Therapeutics. 'We are very pleased to welcome Kylie to the uniQure executive leadership team as we plan for the potential U.S. commercial launch of AMT-130 in 2026,' said Matt Kapusta, chief executive officer of uniQure. 'Kylie brings deep commercial expertise in rare diseases, and her knowledge of Huntington's disease and execution of gene therapy launches will be invaluable as we prepare to transition to a commercial-stage biotechnology company.' Ms. O'Keefe is an accomplished business leader with broad biopharmaceutical experience and a proven track record in rare diseases and gene therapy. Most recently, she served as Chief Commercial Officer at PTC Therapeutics, where she led global commercial strategy, operations and portfolio management for multiple rare neurology and metabolic commercial products across more than 50 countries. During her tenure, Ms. O'Keefe led several strategically significant commercial launches and supported corporate strategy and pipeline development for both small molecules and gene therapies including Upstaza™ (AADC deficiency). She also directed the development and execution of reimbursement strategies, including payer engagement and health economic assessments, and led business development and investor relations. Earlier in her career, Ms. O'Keefe held key roles at LEO Pharma where she launched a portfolio of pharmaceutical products in more than 30 countries. Ms. O'Keefe holds a Bachelor's degree in Biotechnology Innovation from Queensland University of Technology in Brisbane, Australia and a Graduate diploma in Managing Medical Product Innovation from Copenhagen Business School in Frederiksberg, Denmark. 'I am thrilled to join uniQure at such an exciting time for the company,' commented Ms. O'Keefe. 'AMT-130 has the potential to be the first disease-modifying treatment for Huntington's disease. With a clear and aligned path towards accelerated approval in the U.S., uniQure is well positioned to deliver a potentially historic breakthrough in Huntington's disease. I look forward to leveraging my experiences in rare disease and gene therapy, and to working with the talented team at uniQure to advance its mission of addressing the urgent needs of Huntington's patients.' About uniQure uniQure is delivering on the promise of gene therapy – single treatments with potentially curative results. The approvals of uniQure's gene therapy for hemophilia B – an historic achievement based on more than a decade of research and clinical development – represent a major milestone in the field of genomic medicine and ushers in a new treatment approach for patients living with hemophilia. uniQure is now advancing a pipeline of proprietary gene therapies for the treatment of patients with Huntington's disease, refractory temporal lobe epilepsy, ALS, Fabry disease, and other severe diseases. uniQure Forward-Looking Statements This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," 'establish,' "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," 'seek,' "should," "will," "would" and similar expressions. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this press release. Examples of these forward-looking statements include, but are not limited to, statements concerning the Company's commercialization plans; the Company's ability to deliver potentially life-changing therapy to people living with Huntington's disease and related timeline for doing so; the potential clinical and functional effects of AMT-130; and the Company's plans to continue clinical development of AMT-130. The Company's actual results could differ materially from those anticipated in these forward-looking statements for many reasons. These risks and uncertainties include, among others: risks associated with the Company's Phase I/ll clinical trials of AMT-130, including the risk that interim data from the trials may not be predictive of later data readouts that will serve as a basis for further regulatory interactions, may not support a Biologics License Application (BLA) submissions or accelerated approvals, may not be satisfactory to the FDA and other regulators, and new analyses of existing data and results may produce different conclusions than established as of the date hereof; risks related to the Company's current and future interactions with regulatory authorities, which may affect the initiation, timing and progress of clinical trials, its BLA submission plans and pathways to regulatory approval; risks related to the Company's ability to pursue business development efforts with respect to AMT-130; uncertainties as to the FDA's and other regulatory authorities' interpretation of the data from the Company's Phase I/ll clinical trials of AMT-130 and acceptance of the Company's clinical programs and the regulatory approval process; later developments with the FDA and other regulators that could be inconsistent with the feedback received to date; the Company's ability to continue to build and maintain the Company infrastructure and personnel needed to achieve its goals; the Company's effectiveness in managing current and future clinical trials and regulatory processes; the continued development and acceptance of gene therapies; the Company's ability to demonstrate the therapeutic benefits of its gene therapy candidates in clinical trials; the Company's ability to obtain, maintain and protect intellectual property; and the Company's ability to fund its operations and to raise additional capital as needed. These risks and uncertainties are more fully described under the heading "Risk Factors" in the Company's periodic filings with the U.S. Securities & Exchange Commission ('SEC'), including its Annual Report on Form 10-K filed with the SEC on February 27, 2025 and in other filings that the Company makes with the SEC from time to time. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and the Company assumes no obligation to update these forward-looking statements, even if new information becomes available in the future. uniQure Contacts: FOR INVESTORS: FOR MEDIA: Chiara RussoDirect: 617-306-9137Mobile: Tom MaloneDirect: 339-970-7558Mobile: in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
