Trials for Rejuvenation Biotechnology Targeting α-Synuclein

A long and detailed piece from the SENS Research Foundation on the relevance of ongoing development of therapies for Parkinson's disease based on targeting α-synuclein, a protein thought to be important in the disease process:

A range of damaged proteinaceous aggregates accumulate intracellularly and extracellularly in the aging brain, with higher burdens of characteristic aggregates associated with diagnosed age-related neurodegenerative disorders. These include beta-amyloid protein (Aβ) and neurofibrillary tangles (NFT) in Alzheimer's disease (AD) and other age-related dementias, and Lewy bodies and other intracellular α-synuclein (AS) aggregates in Parkinson's disease (PD) and other synucleinopathies. Additionally, it is increasingly clear that LB along with other neuronal protein aggregates are key drivers of "normal" cognitive aging.

Multiple lines of evidence from cell culture studies, transgenic model organisms, and genetic epidemiology link a person's steady-state AS levels and accumulation of LB to both clinical PD and subclinical age-related movement disorders. Mutations and genetic variants that increase the production or aggregability of AS are clearly linked to earlier onset and severity of PD.

Buoyed by the strong evidence from AS vaccination studies, an Austrian biotechnology firm with an unique development platform - with support from a major Parkinson's charity - has lept ahead of the pack. As of this writing, they are now in the midst of human clinical trials of a first-in-class immunotherapeutic agent targeting the removal of pathological AS species as a disease-modifying rejuvenation therapy to prevent, arrest, and reverse the ravages of Parkinson's disease.

The degenerative aging process is driven by the accumulation of multiple forms of cellular and molecular damage in the structures of our tissues, leading progressively over time to increasing disease, disability, and ultimately death. PD as a clinical entity emerges when the level of a specific subset of such lesions crosses of a clinical threshold. The key corollary of these facts is that when rejuvenation biotechnology matures to the point that this underlying damage is safely and effectively removed, repaired, replaced, or rendered harmless, then PD and the full spectrum of age-related disease and disability can be prevented, arrested in its course, and ultimately reversed.

AS vaccines will address one key driver of the PD phenotype: the accumulation of aggregated AS species in the brain and peripheral nervous system. But to fully arrest the progression of the disease, multiple rejuvenation biotechnologies will have to be brought to bear, each of them targeting specific cellular and molecular lesions involved in the constellation of pathology underlying PD.

Step by step, the rejuvenation biotechnologies needed to prevent and reverse the disabling neuropathology that drives PD are being developed, tested in rodents, and moved into clinical trials. The rejuvenation biotechnologies that emerge from these trials will initially be indicated for PD, but the lesions that these new therapies target are suffered by all aging people, driving the universal age-related loss of motor control, cognition, and autonomic dysfunction. Whether any individual suffers the obvious gait disturbances, tremors, and "masklike" loss of facial affect - these eventualities are in part a matter of individual variations in how rapidly the age-related lesions most specific to PD symptoms accumulate in our tissues, and in part a matter of the rate at which other aging damage accumulates in our bodies, overshadowing or pre-empting clinical PD with competiting forms of age-related morbidity and mortality.

An end to this, and to the misery of age-related ill health in all its forms, are what drives SENS Research Foundation's work in research, education, outreach, transdisciplinary networking, and advocacy. We are encouraged by the progress being made in clearance of AS aggregates from the aging brain, moving us one step closer to the day when humanity will move free of the mummification of the years.



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