Researches conducted on certain ayurvedic herbs have provided hope in identifying a set of anti-parkinsonian molecules that might help to design novel drugs for arresting the progression of Parkinson’s disease, according to Dr K P Mohanakumar, scientist, Division of Cell Biology & Physiology at the Indian Institute of Chemical Biology, Kolkata.

Parkinson’s disease (PD) is a progressive neurodegenerative disease, for which symptomatic relief is the only therapeutic strategy, he said while delivering Dr Lalitha Kameswaran Memorial Oration at PSG College of Pharmacy in Coimbatore.

In the ongoing researches for inventing new drugs for treating this progressive neurodegenerative disorder, Dr Mohanakumar said one of the activities being initiated in the country is focused on identification of extracts or mixture of compounds or molecules for use as PD drugs from plant sources that have been listed as medicines in Indian traditional system of medicine. In his institute in Kolkata, his team has investigated carefully some of the herbal components used for treating the PD patients, and identified two classes of molecules contained therein, one of which (phenolic amine derivatives) possessed severe pro-parkinsonian activity and the other (substituted tetrahydroisoquinoline derivatives) exhibited excellent anti-parkinsonian potential. The investigations were carried out as a follow up of a prospective clinical trial of Ayurveda therapy which completed in the year 2000, the scientist said.

When the first type of molecules was administered into rodents, it was found that it caused severe dopamine depletion in the striatum and led to significant behavioural aberrations, leading to anxiety and depression. The latter class protected against MPTP (a neurotoxin that causes permanent symptoms of Parkinson's disease by killing certain neurons in the substantia nigra of the brain) induced behavioural dysfunctions and striatal dopamine loss, which were better than the effects of the anti-parkinsonian drug, Selegiline. The synergistic actions of several molecules present in the traditional preparation could derive significant and better medical benefits to the patient population. However, he said, the accumulated data in their laboratory suggested some complicated mechanisms of actions of Ayurvedic medication.

The major risk factor the scientist has found in his research for the disease is the phenomenon of ageing. The major pathology of the disease is more than 80 per cent loss of the neurotransmitter dopamine in the striatum, resulting from the death of copious number of the neurotransmitter producing cells in the substantia nigra pars compacta region (a densely packed region of cells), but not in ventral tegmental area. Although more than 97 per cent PD population do not have any genetic predisposition, the possibility of epigenetic involvement in the disease is suggested. These in turn have triggered a lot of enthusiasm and interest in PD research in India, and it is heartening to see the close association of clinicians and basic researchers.

Dr. Mohanakumar has pointed out that there have been some changes in the perspectives of the researchers worldwide other than addressing dopaminergic dysfunction that has helped to retard the progression of the disease which resulted in more than five novel drug candidates for the disease.

Another upcoming field of research in PD is regenerative medicine, employing neuronal transplantation. While some laboratories in India resort to studies on autologous transplants in parkinsonian models, the Indian Institute of Chemical Biology in Kolkata uses stem cells which are differentiated into dopaminergic neurons. Stem cells and the differentiated neurons are characterized for implantation into desired regions of the brain. The recovery is monitored in terms of behaviour, cell survival and neurochemistry. One of the major obstacles faced is obtaining desired number of pure dopaminergic neuronal population for transplantation.

Lack of information on the number of cells to be implanted at a given stage of the disease is yet another concern, since severe dyskinesia was one of the major problems in autologous transplantation cases in human studies. It has to be admitted that the process of transplantation recovery research is in the primitive stages, and use of media, growth factors and other reagents in culturing and differentiating the neurons in the in vitro, and are contraindicated for human use is a major stumbling block for introduction of this technology into human patients.