Neurological disorders

Description

As part of our vision to translate neuroscience research into clinical neurological practice, we are targeting neurodegenerative diseases. These disorders represent a growing healthcare, financial, and logistic challenge for the society and the healthcare sector, primarily due to the lack of effective treatment options. Current treatments, though useful for temporary symptomatic relief, do little to prevent disease. Our goal is to continue working with our academic and industry partners to provide therapeutic breakthroughs for these neurodegenerative diseases in their early stages, with a major focus on Alzheimer’s disease, Multiple Sclerosis (MS), motor neuron disease (including ALS), Schizophrenia, and Parkinson’s disease.

 

In addition to neurodegenerative disorders, we are developing new and effective drugs for neuro-oncology. There have been limited therapeutic advances in the field of neuro-oncology, which is a substantial unmet clinical need. We are using an integrative multi-disciplinary approach and cutting-edge translational research to develop novel, curative therapies for primary and metastatic brain cancers.

 

Clinically, we aim to improve the quality of care and enhance the quality of life of neurological patients through better symptom management and interdisciplinary efforts and their caregivers by expanding survivorship and family care services.

 

Our ultimate goal is to efficiently develop effective therapies and improve quality-of-life outcomes for patients with autoimmune disorders and neurological diseases.

 

Alzheimer’s Disease (AD)

 

Alzheimer’s disease is a degenerative brain disease. It is the most common cause of dementia. The characteristic symptoms of dementia are difficulties with memory, language, problem-solving, and other cognitive skills. The resultant is a decline in an individual’s ability to perform everyday activities. These difficulties occur because neurons in parts of the brain involved with cognitive function have been damaged or destroyed.

 

In Alzheimer’s disease, neurons in other parts of the brain are eventually damaged or destroyed as well, including those that enable a person to carry out basic bodily functions such as walking and swallowing. Difficulty in remembering recent conversations, names, or events is often an early clinical symptom: apathy and depression are also often present as early symptoms. Later symptoms include impaired communication, disorientation, confusion, poor judgment, behavior changes, and, ultimately, difficulty speaking, swallowing, and walking. People in the final stages of the disease are bed-bound and require round-the-clock care. Alzheimer’s disease is ultimately fatal.

 

The hallmark pathologies of Alzheimer’s are the progressive accumulation of the protein fragment beta-amyloid (plaques) outside neurons in the brain and twisted strands of the protein tau (tangles) inside neurons. These changes are eventually accompanied by neuronal damage and death. Alzheimer’s disease begins years before the symptoms are clinically presented.

 

The pharmacological intervention (medications) has not shown to decrease the impact (slow or stop), which progressively leads to neuronal damage and destruction. The U.S. Food and Drug Administration (FDA) has approved six drugs for the treatment of Alzheimer’s—rivastigmine, galantamine, donepezil, memantine, memantine combined with donepezil, and tacrine (now discontinued in the United States). These drugs temporarily improve symptoms by increasing the amount of chemicals called neurotransmitters in the brain. The effectiveness of these drugs varies from person to person and is limited in duration.

 

Amyotrophic Lateral Sclerosis (ALS)

 

Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by the

progressive loss of motor neurons in the brain and spinal cord. It is a clinically and

genetically heterogeneous, multi-domain neuro-degenerative syndrome of motor and extra-motor systems with multiple underlying pathophysiological mechanisms. ALS is characterized by progressive motor deficits that develop over the course of weeks and sometimes months. It may affect any voluntary muscle, which means the presentation is heterogeneous, ranging from dysarthria to a foot drop. The onset of the disease is focal in most patients, and over time other regions of the body become affected. The mechanisms underlying degeneration in ALS are still not completely understood.

 

Currently, Riluzole is the only drug that has been shown to prolong survival in ALS. In the absence of effective pharmacological treatments, symptomatic interventions and supportive care remain the cornerstone of ALS management. Owing to the recent demonstration of different pathophysiological mechanisms for ALS, it is likely that the different ALS subtypes respond differently to various therapies. This necessitates applications of the principles of personalized medicine to tailor treatments to different patients based on their disease profiles. Such a modality requires the development of biomarkers for accurately characterizing the disease and targeted therapeutics for the different subtypes.

 

Schizophrenia

 

Schizophrenia is a severe psychiatric disorder with a profound impact on the individual and society. While outcomes may not be as uniformly adverse as is commonly believed, over 50% of those individuals who receive a diagnosis have intermittent but long-term psychiatric problems. Around 20% will experience chronic symptoms and disability. The life expectancy of these individuals is reduced by 10–20 years.

 

Understanding the etiology and pathogenesis of schizophrenia and developing new, more effective, and acceptable treatments remains a significant unmet medical need. It is also one of the most formidable challenges facing modern medicine. Recent advances in genomics and neurosciences are helping to develop better therapeutics.

 

Schizophrenia is characterized by positive symptoms such as delusions and hallucinations, and negative symptoms such as impaired motivation, reduction in spontaneous speech, and social withdrawal. In addition, it is associated with cognitive impairment. The positive symptoms tend to relapse and remit, though some patients experience residual long-term psychotic symptoms. The negative and cognitive symptoms tend to be chronic and are associated with long-term effects on social function. Diagnosis is made solely on the clinical basis of history and examination of the mental state. Currently, there are no diagnostic tests or biomarkers for schizophrenia.

 

Multiple Sclerosis (MS)

 

Multiple sclerosis is the most prevalent chronic inflammatory neurologic disease. It affects over 2 million people worldwide and nearly 400,000 in the United States alone. The annual economic cost of multiple sclerosis in the United States is approximately $10 billion. Currently, there are approved disease-modifying medications that reduce the frequency of transient episodes of neurologic disability in MS. However, there is no curative therapy available for MS, thus making it as a major unmet medical need.

 

Typically, patients with multiple sclerosis present with monocular visual loss due to optic neuritis, limb weakness or sensory loss due to transverse myelitis, double vision due to brain-stem dysfunction, or ataxia due to a cerebellar lesion. The disease usually shows a progression over 10 to 20 years, leading to impaired mobility and cognition. Approximately 15% of patients have a progressive course from disease onset.

 

Pathologically, multiple sclerosis lesions appear throughout the CNS, in the white matter as focal areas of demyelination, inflammation, and glial reaction. Additionally, demyelination in multiple sclerosis also involves gray matter. Spinal cord lesions produce significant clinical deficits. Tissue damage in MS occurs due to a complex and dynamic interplay between the immune system, glia (myelin-making oligodendrocytes and their precursors, microglia, and astrocytes), and neurons. Radiological and recently, blood and CSF biomarkers are being developed for diagnosis and monitoring disease progression.

 

As of December 2017, the US FDA has approved 15 medications for modifying the course of multiple sclerosis: 5 preparations of interferon-beta; 2 preparations of glatiramer acetate; the monoclonal antibodies natalizumab, alemtuzumab, daclizumab, and ocrelizumab (the first B-cell–targeted therapy); the chemotherapeutic agent mitoxantrone; and the small-molecule oral agents fingolimod, dimethyl fumarate, and teriflunomide. Dalfampridine has been approved as a symptomatic therapy to improve walking speed.

Autism Spectrum Disorders (ASDs)

 

Autism spectrum disorders are a group of neurodevelopmental disorders characterized by impairments in social interaction and communication, as well as repetitive behaviors and restricted interests. These are early-appearing social communication and behavioral deficits that have an active genetic component as well as other causes.

 

In spite of its high prevalence, there is no definitive consensus in the scientific community about the etiology of ASD. Genetics and neuroscience have identified intriguing patterns of risk, but without much practical benefit yet. Considerable work is still needed to understand how and when behavioral and medical treatments can be effective, and for which children, including those with substantial co-morbidities. It is also important to implement what we already know and develop services for adults with ASD.

 

The outlook for many individuals with ASD today is better than it was before. Many individuals with ASD can speak, read, and live in the community rather than in institutions. In fact, some are mostly free from symptoms of the disorder by adulthood. Nevertheless, most individuals will not work full-time or live independently.

 

Clinically, it is beneficial to provide timely intervention and individualized therapy to patients and their families, and by anticipating transitions such as family changes and school entry and leaving.

 

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