Impact of neurodegenerative diseases

Effective treatment of neurodegenerative diseases remains one of the greatest challenges in modern medicine. Many of these diseases are life-threatening. Even if not fatal, they may cause debilitating symptoms and personality changes that are life‑changing for patients and family members. There are many treatments available aimed at managing symptoms; however, to date, none can stop or reverse disease progression. Our mission is to meet this need by developing therapies that target the root causes of these diseases.

Parkinson’s disease, Lewy body dementia and multiple system atrophy are summarized in the term alpha-synucleinopathy characterized by the accumulation of the protein aSyn in neuronal (PD. LBD) and non-neuronal (MSA) cells the brain.18

Parkinson’s Disease

Parkinson’s disease is a life-threatening neurodegenerative disease that results from a progressive loss of nerve cells in the brain.1,2 A diagnosis of Parkinson’s disease is life-changing for patients, as increasingly debilitating and distressing problems with movement and mental function can develop.1,2 As the disease progresses, patients may require assistance for most activities of daily living, which places a profound emotional and physical strain on family members.1

Although the exact cause of the disease is not fully understood, there is compelling evidence that abnormal deposition of the α-synuclein protein, which is toxic to nerve cells, plays an important role.3

Impact on patients

The progressive symptoms of Parkinson’s disease have a profound impact on the lives of patients. Symptoms include shaking, slow movement, stiff and inflexible muscles, instability, depression, memory loss, sleeping problems, and personality changes.1,2 While the average age at onset is 60 years, some patients are diagnosed much younger.4 This means that a patient’s ability to work may be compromised, as it becomes increasingly difficult to perform daily tasks. Parkinson’s disease can deprive patients of recreational activities that they previously enjoyed, and eventually of their independence

Prevalence

An estimated 7–10 million people worldwide live with Parkinson’s disease5

Impact on family members

Parkinson’s disease places substantial physical, emotional, and financial strain on family members.1 As the disease progresses, a patient’s personality may change,1 which may be particularly distressing for family members. In the final stages of the disease, patients may need assistance for most activities of daily living1

Current treatments

Current treatments are aimed at managing symptoms and maintaining the quality of life of patients for as long as possible; however, there is no treatment that can stop disease progression.6 Treatments often have side effects, which may also require management.1,6 Over time, the need for medication may increase, and adherence to progressively complex dosing regimens may become difficult as a result1,7

New therapies

New therapies for Parkinson’s disease are urgently needed in order to address the root causes of this debilitating disease. We are investigating the use of SAIT to specifically target oligomeric species of α-synuclein protein, which are thought to be the toxic forms of the protein, with the aim of reducing the progression of Parkinson’s disease

Huntington’s Disease

Huntington’s disease is a life-threatening neurodegenerative disease that has a profound impact on both patients and family members.8–10 Patients with Huntington’s disease suffer from increasingly debilitating problems with movement, cognition, and psychiatric function.8–10 During the later stages of the disease, patients may not be able to walk, speak, or swallow food, as they become dependent on caregivers.8–10 The symptoms usually first appear at 30–50 years of age, and it normally leads to death within 10–30 years of symptom onset.9

Huntington’s disease results from inheriting a mutated version of the huntingtin gene; the resultant faulty huntingtin protein (mutHTT) induces a progressive loss of nerve cells in certain parts of the brain, leading to the development of symptoms.8,10,11

Impact on patients

The progressive symptoms of Huntington’s disease have a profound impact on the lives of patients. Symptoms include memory lapses, depression, personality changes, and movement difficulties.8 Symptoms may affect a patient’s ability to work, perform daily tasks, and take part in recreational activities that they used to enjoy. The behavior of patients may become erratic and they may suffer from mood swings8,11

Prevalence

An estimated 3–7 per 100,000 people of European ancestry are affected by Huntington’s disease10

Impact on family members

Huntington’s disease places substantial physical, emotional, and financial strain on family members.8,10 The knowledge of a familial genetic predisposition and the effects of the disease on mental health can be particularly distressing for family members, as they may see their loved one develop mood swings and personality changes.8 Patients may become dependent on caregivers before they reach old age8,10

Current treatments

Current treatments aim to ease the symptoms of Huntington’s disease; however, there is no treatment that can stop disease progression.8 Additionally most of these treatments can cause troublesome side effects12

New therapies

New therapies for Huntington’s disease are urgently needed to address the root cause of this debilitating disease. We are investigating the use of SAIT to target mutHTT, with the aim of reducing the progression of Huntington’s disease

We are developing not only SAIT but also a novel monoclonal antibody therapy for treating Huntington’s disease. Both these approaches are entering the preclinical phase of development. If you wish to learn more about this approach, please contact us.

MULTIPLE SYSTEM ATROPHY

Multiple system atrophy (MSA) is a rare neurodegenerative disease that is caused by the progressive loss of nerve cells in the brain and spinal cord.1 Typically MSA impairs the patient’s autonomic nervous system that is essential for controlling blood pressure and body temperature, digestion, urination, and sexual function as well as movement.2 Symptoms are worsening continuously with rapid progression at the onset with a mean survival time of 6-10 years.3 MSA is usually diagnosed based on symptoms, but should not be confused with Parkinson’s disease although early signs and symptoms are similar.4

Like for Parkinson’s disease the cause of MSA is unknown. However, pathological accumulation of the protein alpha-synuclein (aSyn) is observed in glial brain cells. This clumps of aSyn is thought to be responsible for brain damage leading to motor and non-motor symptoms.5

Impact on patients

Disease onset typically occurs in the sixth decade of life. Within 3 years of onset of motor symptoms about half of the patients need a walking aid, within 5 years 60% of the patients a wheelchair. On average patients are bedridden within 6-8 years.6

Prevalence

The estimated prevalence is 3.4 to 4.9 cases per 100,000 population translating into about 14,000 people currently living with MSA in the US, about 22,000 in the EU and about 67,000 in East Asia. The estimated incidence is 0.6 to 0.7 cases per 100,000 population, meaning here are every year about 2.000 new cases in the US, about 3,000 in the EU and about 10,000 in East Asia.7

Current treatments

There is no medication slowing down the progression of the disease nor any cure. Treatments available are targeted at symptoms like low blood pressure, or problems with bladder control, sleep or swallowing. Levodopa which is used in patients with Parkinson’s disease may help at an early stage with motor symptoms but will lose its benefit with the progression of the disease.8

New therapies

New therapies for MSA are urgently needed to address the root cause of this debilitating disease. We are investigating the use of SAIT to specifically target oligomeric species of α-synuclein protein, which are thought to be the toxic forms of the protein, with the aim of reducing the progression of MSA.

References

1. National Institute of Health (NIH). National Institute of Neurological Disorders and Stroke (NINDS). Multiple System Atrophy Factsheet. 13 August 2018.  https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Multiple-System-Atrophy; accessed 16 Oct 2019

2. Multiple System Atrophy Coalition. About MSA.  https://www.multiplesystematrophy.org/about-msa/; accessed 16 Oct 2019

3. Fanciulli A., Wenning G.K. Multiple System Atrophy.  N Engl J Med 2015; 372:249-63.

4. National Health Service (NHS). Conditions, Multiple system Atrophy. 7 August 2017. https://www.nhs.uk/conditions/multiple-system-atrophy/; accessed 16 Oct 2019

5. National Health Service (NHS). Conditions, Multiple system Atrophy. 7 August 2017. https://www.nhs.uk/conditions/multiple-system-atrophy/; accessed 16 Oct 2019

6. Fanciulli A., Wenning G.K. Multiple System Atrophy.  N Engl J Med 2015; 372:249-63.

7. Fanciulli A., Wenning G.K. Multiple System Atrophy.  N Engl J Med 2015; 372:249-63.

8. National Institute of Health (NIH). National Institute of Neurological Disorders and Stroke (NINDS). Multiple System Atrophy Factsheet. 13 August 2018.  https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Multiple-System-Atrophy; accessed 16 Oct 2019

LEWY BODY DEMENTIA

 

Lewy body dementia is a neurodegenerative disease that is characterized by the abnormal accumulation of the protein alpha-synuclein (aSyn) in the brain. These accumulations are called Lewy bodies. In addition to Lewy bodies also amyloid plaques, normally present in brains of Alzheimer’s disease patients, are found in the brains of DLB patients. Both protein pathologies are thought to affect thinking, movement, behaviour, and mood.1 As the diseases progresses activities of daily living will become more and more difficult for patients who will subsequently require assistance.2 Onset of the disease is usually sometime at the age of 50 or older and survival time is on average 5 to 8 years, ranging from 2 to 20 years.3

While the precise cause of LBD is unknown, it is understood that the deposits of Lewy bodies and amyloid plaques lead to the loss of neurons that are producing two neurotransmitters: one, acetylcholine, affects the ability for memory and thinking, the other, dopamine, affects behaviour, mood, motivation, cognition, and sleep.4

Impact on patients

Symptoms in the early stage of LBD can be mild but worsen with progression of the disease as the patient’s movement and thinking abilities decline. Patients may experience signs of parkinsonism like muscle rigidity, tremor, and balance problems, or cognitive symptoms like dementia, cognitive fluctuations or hallucinations.5

Prevalence

The WHO estimates that there are worldwide about 50 million people living with dementia. Every year, there are 10 million new cases.6 LBD may account for 10-15% of these cases, but is often misdiagnosed for Alzheimer’s.7

Current Treatments

There is no medication slowing down the progression of the disease nor any cure. Available treatments to treat certain LBD symptoms must be carefully considered as they might have a negative effect on other LBD symptoms. Cognitive symptoms may be treated with medications developed for Alzheimer’s disease, movement disorders with medications used for Parkinson’s disease.

New Therapies

New therapies for DLB are urgently needed to address the root cause of this debilitating disease. We are investigating the use of SAIT to specifically target oligomeric species of α-synuclein protein, which are thought to be the toxic forms of the protein, with the aim of reducing the progression of DLB.

References

1. National Institute of Health (NIH), National Institute of Aging (NIA). Health information, what is Lewy body dementia? 27 June 2018.  https://www.nia.nih.gov/health/what-lewy-body-dementia. Accessed 16 October 2019

2. National Health Service (NHS). Overview, Dementia with Lewy bodies. 13 December 2016. https://www.nhs.uk/conditions/dementia-with-lewy-bodies/; accessed 16 October 2019

3. National Institute of Health (NIH), National Institute of Aging (NIA). Health information, what is Lewy body dementia? 27 June 2018.  https://www.nia.nih.gov/health/what-lewy-body-dementia. Accessed 16 October 2019

4. National Institute of Health (NIH), National Institute of Aging (NIA). Health information, what is Lewy body dementia? 27 June 2018.  https://www.nia.nih.gov/health/what-lewy-body-dementia. Accessed 16 October 2019

5. National Institute of Health (NIH), National Institute of Aging (NIA). Health information, what is Lewy body dementia? 27 June 2018.  https://www.nia.nih.gov/health/what-lewy-body-dementia. Accessed 16 October 2019

6. World Health Organization (WHO). Fact Sheets, Dementia. 19 September 2019. https://www.who.int/news-room/fact-sheets/detail/dementia; accessed 16 October 2019

7. Alzheimer’s Society UK. Dementia with Lewy bodies: what is it and what causes it? https://www.alzheimers.org.uk/about-dementia/types-dementia/dementia-with-lewy-bodies; accessed 16 October 2019

References

  1. World Health Organization (WHO). Neurological disorders associated with malnutrition. In: Neurological Disorders: public health challenges. 2006. http://www.who.int/mental_health/neurology/chapter_3_b_neuro_disorders_public_h_challenges.pdf?ua=1. Accessed 15 January 2019
  2. National Health Service (NHS). Overview. Parkinson’s disease. 9 June 2016. https://www.nhs.uk/conditions/parkinsons-disease/. Accessed 15 January 2019
  3. Stefanis L. α-synuclein in Parkinson’s disease. Cold Spring Harb Perspect Med 2012;2(2):a009399
  4. Michael J. Fox Foundation for Parkinson’s research. Parkinson’s disease causes. https://www.michaeljfox.org/understanding-parkinsons/living-with-pd/topic.php?causes. Accessed 15 January 2019
  5. Parkinson’s News Today. Parkinson’s disease statistics. 2018. https://parkinsonsnewstoday.com/parkinsons-disease-statistics/. Accessed 15 January 2019
  6. National Health Service (NHS). Treatment. Parkinson’s disease. 9 June 2016. https://www.nhs.uk/conditions/parkinsons-disease/treatment/. Accessed 15 January 2019
  7. Neurology Times. Parkinson medication adherence is suboptimal. 17 February 2015. http://www.neurologytimes.com/parkinson-disease/parkinson-medication-adherence-suboptimal. Accessed 15 January 2019
  8. National Health Service (NHS). Overview. Huntington’s disease. 13 February 2018. https://www.nhs.uk/conditions/huntingdons-disease/. Accessed 15 January 2019
  9. National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS). Huntington’s disease information page. 15 June 2018. https://www.ninds.nih.gov/Disorders/All-Disorders/Huntingtons-Disease-Information-Page. Accessed 15 January 2019
  10. Huntington’s Disease Foundation. Life with Huntington’s disease. 2017. http://www.huntingtonsdiseasefoundation.org/life-with-hd-1. Accessed 15 January 2019
  11. National Health Service (NHS). Symptoms. Huntington’s disease. 13 February 2018. https://www.nhs.uk/conditions/huntingtons-disease/symptoms/. Accessed 15 January 2019
  12. National Health Service (NHS). Treatment and support. Huntington’s disease. 13 February 2018. https://www.nhs.uk/conditions/huntingtons-disease/treatment/. Accessed 15 January 2019
  13. National Institutes of Health (NIH), National Institute on Aging (NIA). Alzheimer’s disease fact sheet. 17 August 2016. https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet. Accessed 15 January 2019
  14. National Institute on Aging (NIH). What happens to the brain in Alzheimer’s disease. 2017. https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease. Accessed 15 January 2019
  15. Crews L, Tsigelny I, Hashimoto M, Masliah E. Role of Synucleins in Alzheimer’s disease. Neurotox Res 2009;16(3):307–317
  16. Alzheimers.net. 2017 Alzheimer’s statistics. 2018. https://www.alzheimers.net/resources/alzheimers-statistics/. Accessed 15 January 2019
  17. Verdict Hospital (GlobalData Healthcare). Aging population expected to increase the prevalent cases of Alzheimer’s disease. 2 March 2018. https://www.hospitalmanagement.net/comment/aging-population-expected-increase-prevalent-cases-alzheimers-disease/. Accessed 15 January 2019
  18. Tiago F. Outeiro et al. Dementia with Lewy bodies: an update and outlook. Mol Neurodegeneration (2019) 14:5