Professional Documents
Culture Documents
Alzheimer's
Goal of Clinical Research are to SLOW or STOP
disease progression and PREVENT Alzheimer's
disease.
So early diagnosis is essential and various
initiatives are underway to identify at risk
individual, enable early diagnosis and track
treatment.
Genetics of Alzheimer's Disease
1. Early-Onset AD
Early-onset AD is a rare form of AD, affecting only about 5 percent
of all people who have AD. It develops in people ages 30 to 60.
1 2 3
Neurons are internally supported by microtubules
and TAU protein help in stabilizing microtubules.
In Alzheimers TAU is hyperphosphorylated and
this leads to clumping of neurons.
Changes in brain
Amyloid plaques
Tau tangles
Other abnormal protein deposits
Reduced oxygen flow to tissues
Toxic processes
Four main strategies in anti- amyloid therapy
1. Immunotherapy ( active and passive ) to modify
the process by which Amyloid beta is converted to
senile plaque.
2. Secretase inhibitors
3. Selectively reduce beta amyloid 42, by shifting
production to less toxic 38 and 40.(tarenflurbil)
4. Inhibit aggregation of Amyloid beta, inhibiting
plaque formation. (tramiprosate- GAG)
The advances in our knowledge about the
mechanisms and risk factors associated with AD
have expanded the types of interventions under
study. These trials are examining a host of
possible interventions, including cardiovascular
treatments, hormones, type 2 diabetes
treatments, antioxidants, omega-3 fatty acids,
immunization, cognitive training, and exercise,
among others.
Summary about the our present understanding of Alzheimer's
Previous works have shown a number of attributes shared by both familial and
sporadic AD. Mutations in the genes for b APP, presenilin-1 or -2, account for
nearly all of the early-onset familial cases of AD. Most late-onset AD is sporadic
yet subject to genetic influences, including the e 4 allele of apolipoprotein E and
a haplotype of polymorphisms in proinflammatory cytokine loci. Therefore, the
ongoing development or pathogenesis of the disease is clearly a complex
pathway involving numbers of complex mechanisms, most likely both genetic
and physiological. New pathogenic mechanisms continue to be suggested by
various methodologies. Most hypotheses include an overproduction or
accumulation of the 42-amino acid form of the amyloid b -peptide, produced
from b APP by the b - and g -secretases. However, there is also evidence for
aberrant phosphorylation, non-enzymatic glycosylation, oxidation, nitrosylation,
and other posttranslational modifications of multiple proteins. Thus, critical
insights might be gleaned from additional understanding of protein levels and
alterations.
Phase 1 trials: Small studies in healthy volunteers
or patients that identify drug effects, measure side
effects of different doses, and explore efficacy.
( finding safe dose)
SB742457
SB742457, a small-molecule antagonist of 5-HT6, is
in the second round of Phase II testing. In preclinical
studies, antagonists of 5-HT6 were found to variably
enhance cholinergic, glutamatergic, noradrenergic,
and dopaminergic neurotransmission; in human studies,
they were associated with benefit in terms of several
tests of learning and memory.
SK-PC-B70M
SK-PC-B70M is composed of the oleanolic glycoside
saponin–enriched fraction of Pulsatilla koreana (Korean
pasque flower), which has been found to have
neuroprotective and cognition-enhancing effects in animal
models. A Phase II study in patients with mild to
moderate AD was completed in January 2009.
Omega-3 Fatty Acids