Sunday, June 24, 2012

New Oral MS drug Reduces Brain Lesions

From the 2012 AAN annual meeting, ONO-4641, a potent selective sphingosine-1-phosphate (S1P) receptor agonist (two other similar drugs are Fingolimod...already FDA approved... and BAF), was found to reduce the number of lesions on MRI in patients with the relapsing remitting form of MS.The drug was well tolerated with no unexpected adverse events. Those adverse events were dose related cardiovascular ones. The phase 2b study of ONO-4641 shows that lower doses will be safer.

Monday, June 18, 2012

Impaired Cognitive Function in Asymptomatic Carotid artery Disease

From the International Stroke Conference, Dr. C. Balucani enrolled 330 patients from 2005-10. In each of four evaluations, patients with bilateral internal carotid artery stenosis showed significant impairments in both brain hemispheres compared to controls.Patients with unilateral stenosis showed significant impairment only in the brain hemisphere connected to the embarrassed vascular supply.

Memories Blocked..but Recall Restored

HDAC2 ( histone deacetylase 2 ) regulates the expression of genes involved in learning and memory. MIT scientists led by Li-Huei Tsai,PhD blocked the buildup of HDAC2 in a mouse model of Alzheimer's disease and it restored structural and synaptic plasticity allowing mice with symptoms of AD to restore and access memory. This experiment suggests that memories of things learned may still be stored in the brain but overproduction of HDAC2 blocks access to those memories. This finding has already been experimentally replicated.
In another epigenetic part of their study, these researchers found that glucocorticoid receptor 1normally turned on by stress was in fact switched on/activated from the accumulation of Abeta amyloid causing an increase in HDAC2 and chronic blockage of the genes necessary for memory.
For alzheimer's patients , these MIT researchers have developed a potent HDCA2 inhibitor and are preparing to submit papers to the FDA to begin experimental testing.
NATURE 2012 ; 483 (7388):222-226
Also see Science 2012;335(6075):1513-1516 "Generation of a synthetic memory trace"

Sunday, June 17, 2012

Potential Treatment for Alzheimer's Disease :Bexarotene

I have been in email communication with the lead investigator Gary Landreth,Ph.D. of Case Western Reserve University ( my father's alma mater ) in my home town of Cleveland, OH as I am very excited about his preliminary findings in using bexarotene ( Targretin ) in mouse models of Alzheimer's disease. This drug has been FDA approved for the treatment of cutaneous T-cell lymphoma, has been in use in humans in this capacity for 10 years and has a favorable safety profile.
In this experiment led by Paige E. Cramer, after a 14 day treatment period, there was a sustained 30% reduction in soluble amyloid-beta levels and a 75% reduction in amyloid-beta plaques ! More to come.....
( Science 2012 Feb 9 )

Double Edged Sword: AMYVID

Amyvid ( florbetapir F18 Injection) was approved by the FDA on April 10th for the imaging of amyloid using positron emission tomography (PET) in adults being evaluated for Alzheimer's disease. The problems : what constitutes a definitively abnormal scan ? If a scan reveals significant amyloid burden, then what ? CSF biomarkers can aid the neurological exam and establish a diagnosis with better than ever sensitivity, but then what ? As we have no definitive cure for the disease......stay tuned as hope is on the horizon !
PS. This test is not currently covered by Medicare...cost to consumer $3000.00

Friday, June 15, 2012

A WORLD'S FIRST: A Parkinson's Vaccine

Phase I study of the AFFIRIS AG Parkinson's candidate PD01A has begun.PD01A targets alpha-synuclein and induces antibodies to neutralize its toxic impact potentially modifying the diseases course. This is a "First-in-man""First-in kind"trial that will enroll 32 patients to be the pioneers of this immunotherapy of Parkinson's disease.

Dizziness Update

HC-BPPV ( apogeotropic horizontal canal benign paroxysmal positional vertigo ) Tx=Gufoni maneuver
Neurology 2011; E-pub Dec 14

MS Update in Pregnancy

Multiple Sclerosis
Glatiramer acetate = in pregnancy
Continuum 2010;16(5):193-210
Rebif 22 mcg sc qod then 44mcg
(Interferon beta 1-a)
REFLEXION study sc beta I nterferon-1a 44mcg 3X/wk ...early(AAN2012)

Dementia Update Cliffnotes

Dementia with Lewy body DLB=
Decreased CSF alpha- synuclein
AD=Decreased CSF amyloid-beta 42 (earlier bio-mkr) ⬆total-tau and phospho-tau
Increased soluble amyloid precursor protein beta (sAPP) (Neuro 77;1:7/11)
DLB and AD = 80 % Diagnostic sensitivity
AD with Lewy body pathology 35-40% Diagnostic sensitivity

Brain 2010 Sept 7 2011.......
P300 < 323ms ,>5.0 mV = nml
E. Braverman, Cornell/Harvard
DRUG Treatment of Psychiatric consequences of DementingIllness
1. Impulsive Tx (stealing, sexual) : (Zoloft) sertraline 200mg/d, lamictal, VPA,divalproex,Inderal
2. Agitation /Paranoia : trazodone
3. Delusional : risperidone (ie. delusion of theft)
Mild Cognitive Impairment Treatment
MCI (Neurology 1/10/12 Vanderbilt nicotine patch 15 mg/d...cotinine is the active ingredient (from tobaccoJrnlAD) 2/14/11

CDR ( Clin. Dementia rating scale ) Wash U. St. Louis
CDR 3=severe,CDR2=mod, 1=mild,0.5 very mild

PET in diff dementia PLoS One 2011;6(3):e18111

DBS of entorhinal cortex enhances memory in MCI --( NEJM 2012;366:502-510)

✳FTD ( frontotemporal degeneration )
1. Progranulin Blood Test (A@G Pharma) ⬇Progranulin in blood dt Progranulin gene (PGRN) mutation ( Nature 2006)
2.C9ORF72 mutation(Neuron2011;72:245-56;257-68)(Lancet Neurol.3/9/12)

Alzheimer's Disease ⬆plasma Adiponectin (ArchNeurol2012Jan1)

Parkininson's Treatment Breakthrough

CLR01....a C-shaped complex molecular compound that wrap around the chains of lysine of alpha-Synuclein aggregates removing them. A process-specific mechanism employing transgenic zebra fish model of PD ( A tropical freshwater fish )