When there is a progressive loss of neurons structurally or functionally, sometimes even their death, it is collectively known as neurodegeneration. This precipitates into difficulty in movement and mental functioning (i.e. ataxia and dementia). Diseases such as Parkinson's, Alzheimer's and Huntington's etc fall in this category and are known as neurodegenerative diseases [1], [2].

DATA ON NEURODEGENERATIVE DISEASES:

1. In Alzheimer's disease, 5-10% of individuals above the age of 65 and 30% of them above the age of 85 suffer from dementia.

2. Alzheimer's disease is an abnormal part of the aging process seen in the elderly.

3. Parkinson's disease presents itself in 3% of the population above 65 years of age.

4. It is also wrongly diagnosed in 24% of the population [3].


NEW AGE THERAPIES:

1. Antibody therapy: The signs of Alzheimer's disease in the brain are plaques made up of Aβ protein aggregates & neurofibrillary tangles (NFTs). Incorporation of antibodies against Aβ and tau is by far the most innovative treatment for AD. The data from preclinical studies has been promising; hence, 13 Aβ immunotherapy trials are underway, the world over. The animals gave out a strong immune response variably in the preclinical phase- passive Abs immunotherapy was adopted which brought down the level of plaques already formed along with the Aβ levels, neuritic dystrophy and behavioral deficits. Another solution to many of the immune & inflammatory diseases is the intravenous immunoglobulin (IVIg) injection approved by the USFDA. The positive aspect is that the results of epidemiologic and early clinical tests are in favour of IVIg use but the downside is that only a small percentage of the mixture is constituted by anti-Aβ Abs. Secondly, the peak efficacy levels of these Abs haven't been determined yet.

A very recent addition to the target bank of immunotherapy in AD is the NFT containing hyper-phosphorylated tau. This treatment approach is still to be tried in a true mouse model of AD (anti-tau immunotherapy).

In Parkinson's disease, the protein a-synuclein is present in the Lewy body inclusions. Immunotherapy research carried out till now involves active immunization with human a-synuclein for 8 months in a mouse model over-expressing human a-synuclein.

When a normal glutamine repeat in exon 1 of the huntingtin protein (Htt) expands, the result is an autosomal dominant, neurodegenerative disease known as Huntington's disease. Most of the treatment options manage the symptoms instead of modifying the disease itself. A more specific choice is developing Ab-based treatment against the mHtt protein that can either prevent the onset or HD progression; the brain pathology of mice did not change after being subjected to this treatment.

Intrabodies also contribute significantly in the treatment of AD, PD and HD as they are antibody fragments that are expressed intracellularly and composed of antigen recognition domains [4].

2. Stem cells for diseases of the central nervous system (CNS) such as Alzheimer's disease (AD), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) - exist as replacement or protective therapy. Adult stem cells have a great advantage in autologous treatment procedures as their harvest and usage can be carried out in the same individual, taking away the ethical issues and risks that are associated with Embryonic Stem Cells (ESCs). Neural stem cells (NSCs) in the adult CNS provide a great impetus in the treatment of neurodegenerative diseases. The above mentioned diseases require individual attention with respect to their pathology and stem cell therapies.

At present, cholinesterase inhibitors are used for treating AD which alleviates only its symptoms. Varied effects of the drug can be seen among AD patients. Approximately, there would be 615,000 new cases of AD by 2029 and 959,000 by 2050. Hence, there is an urgent requirement for curing this disease. Prior to stem cell transplantation, Amyloid Precursor Protein (APP) levels have to be brought down to improve therapeutic efficiency (their increased amounts lessen NSCs, in turn increasing a patients' chances of suffering from AD).

When one loses dopaminergic neurons inside the substantia niagra, motor function is lost leading to the development of a neurodegenerative disease, namely, Parkinson's disease. Therapy for PD covers drug administration & surgery; these drugs treat only the surviving dopamine neurons leaving the rest to die. One of the probable options to treat PD is the MSCs; even NSCs have been incorporated in the process. To achieve a high success rate in PD cell replacement treatment procedures, the appropriate selection of midbrain dopaminergic (mDA) cell lineage is a must.

In Amyotrophic Lateral Sclerosis (ALS), a patient suffers from progressive paralysis due to the death of upper and lower motor neurons. Researchers have still not been able to find out the cause of this disease. Various studies demonstrate that transplanted cells in the cervical spinal cord offer a positive treatment option in ALS, to slow down focal motor neuron loss.

An autoimmune disease of the CNS, Multiple Sclerosis, progresses without the phenomena of relapse (seen only in the initial stages). The occurrence of this disease is higher in young females, in which degradation of myelin sheath occurs. MS presents itself over a broad spectrum i.e. benign to debilitating. At present, the means by which the MS patients are treated encompass monoclonal antibodies, chimeric molecules and hematopoietic stem cells (HSCs) [5].

3. Gene therapy for Sanfilippo Syndrome A: A neurodegenerative disease that occurs when the gene is mutated, encoding the enzyme sulfamidase is termed as Sanfilippo Syndrome type A or Mucopolysaccharidosis type IIIA (MPSIIIA). A substance glycosaminoglycan cannot be broken down, if there is deficient production of the necessary enzyme (due to the mutated gene). This may result in neuroinflammation and dysfunctional organs (most important being the brain). Neurodegeneration occurs leading to speech loss and motor coordination, hyperactivity etc and such children die upon reaching adolescence.

Till now, pre-clinical studies using gene therapy have been performed in mice and dogs. A single shot of the adenoassociated viral vector is surgically injected inside the cerebrospinal fluid, where the brain cells and those in the spinal cord are genetically modified to generate sulfamidase [6].

ALTERNATIVE THERAPIES:

1. Nutritional therapy for pediatric neurodegeneration: A pediatric neurodegenerative disorder, Ponto-cerebellar hypoplasia, presents itself in children with shrunk cerebellum and brain stem over a period of time; breathing, swallowing are the initial complaints culminating in functional disorders and cognitive dysfunction. The mutated gene in question is AMPD2 that gives rise to the ATP - GTP imbalance i.e. neurodegeneration.

Scientists at the Howard Hughes Medical Institute have stumbled upon AICAR, a non-toxic performance enhancing drug, to restore the neurodegenerational imbalance. But there is a word of caution: the adverse effects of the drug in humans have still to be found out [7].

2. Complementary and alternative medicines:
Traditional Chinese medicine uses Ginkgo biloba to improve memory in humans, its important components being ginkgolides, bilobalide, ginkgolic acids and ginkgo flavone glycoside. Two main extracts of the biloba tree- EGb761 and terpene lactone, exhibit their neuroprotective effects on the affected patients.

Also, it has been found that laser acupuncture at HT7 acupoint stops memory impairment non-invasively.

In PD, acupuncture plus Yin Tui Na massage offers relief to such patients.

Tai chi, Reflexology and Aromatherapy are the other methods to protect neurodegeneration in PD patients [8].

REFERENCES:

1. http://en.wikipedia.org/wiki/Neurodegeneration

2. http://www.neurodegenerationresearch.eu/about/what/

3. Soong B. Neurodegenerative diseases (Dept Neurology). Website:
http://bml.ym.edu.tw/ibs/brain/curricurium/1001curricurium/Neurodegenerative%20Diseases%2020120110.pdf

4. Southwell A L, Patterson P H. Antibody therapy in Neurodegenerative disease. Reviews in the Neurosciences. 2010; 21: 273-287.

5. Dantuma E, Merchant S, et al. Stem cells for the treatment of neurodegenerative diseases. Stem Cell Research & Therapy. 2010; 1:37.

6. Ayuso E, Bosch F, et al. Whole body correction of Mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy. Journal of Clinical Investigation. 2013.

7. http://www.foxnews.com/health/2013/08/01/nutritional-therapy-could-potentially-treat-childhood-neurodegenerative-disease/

8. Bhugun V, Chutterdharry G, et al. Complementary and Alternative medicines use against neurodegenerative diseases. Advances in Pharmacology and Pharmacy. 2013; 1(3): 103-123.



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