Rapamycin: Prevention&Treatment of Aging and Age-Related Disease

Rapamycin: Prevention&Treatment of Aging and Age-Related Disease Rapamycin: Prevention&Treatment of Aging and Age-Related Disease Rapamycin: Prevention&Treatment of Aging and Age-Related Disease
  • Home
  • Disease A
    • Cancer
    • Atherosclerosis
    • Cardiomyopathy
    • Age-related Obesity
    • Fatty Liver (NAFLD)
    • Osteoarthritis
    • Diabetes
    • Hypertension
    • Hearing Loss
  • Disease B
    • BPH
    • Osteoporosis
    • Macular Degeneration
    • COPD
    • Chronic Renal Disease
  • Neurodegeneration
    • Normal Aging Brain
    • Alzheimer's Disease
    • Parkinson's Disease
    • Tauopathy
  • Archive
    • Diseases
    • Side Effects
    • Misc
  • References
  • More
    • Home
    • Disease A
      • Cancer
      • Atherosclerosis
      • Cardiomyopathy
      • Age-related Obesity
      • Fatty Liver (NAFLD)
      • Osteoarthritis
      • Diabetes
      • Hypertension
      • Hearing Loss
    • Disease B
      • BPH
      • Osteoporosis
      • Macular Degeneration
      • COPD
      • Chronic Renal Disease
    • Neurodegeneration
      • Normal Aging Brain
      • Alzheimer's Disease
      • Parkinson's Disease
      • Tauopathy
    • Archive
      • Diseases
      • Side Effects
      • Misc
    • References

Rapamycin: Prevention&Treatment of Aging and Age-Related Disease

Rapamycin: Prevention&Treatment of Aging and Age-Related Disease Rapamycin: Prevention&Treatment of Aging and Age-Related Disease Rapamycin: Prevention&Treatment of Aging and Age-Related Disease
  • Home
  • Disease A
    • Cancer
    • Atherosclerosis
    • Cardiomyopathy
    • Age-related Obesity
    • Fatty Liver (NAFLD)
    • Osteoarthritis
    • Diabetes
    • Hypertension
    • Hearing Loss
  • Disease B
    • BPH
    • Osteoporosis
    • Macular Degeneration
    • COPD
    • Chronic Renal Disease
  • Neurodegeneration
    • Normal Aging Brain
    • Alzheimer's Disease
    • Parkinson's Disease
    • Tauopathy
  • Archive
    • Diseases
    • Side Effects
    • Misc
  • References

Age-related Macular Degeneration

Possibility of prevention with Rapamycin

"Age-related macular degeneration (AMD) is a leading cause of irreversible blindness among people of 50 year or older". [Ref 1]  Current therapy is two drugs, Lucentis and Avastin. They are both monoclonal antibodies against VEGF (vascular endothelial growth factor). "Both agents are used for intravitreal injections, which is both cumbersome for patients and is not suitable for preventive treatment." [1] "Because diseases such as AMD are difficult to cure once they have developed, early chemoprevention is likely the best option." [1] The following study showing that rapamycin prevents the progression of AMD in a animal model "provides a new hope for the high risk AMD population".[1]

Rat Model AMD and Rapamycin prevention

The following study, "Prevention of age-related macular degeneration-like retinopathy by rapamycin in rats" [2] is a combined Russian and American study under direction of MV Blagosklonny. They developed a rat model of OXYS rats that developed very early spontaneous AMD and appeared to be an excellent physiological model of human AMD.


The OXYS rats were divided into 2 groups, a control group and a rapamycin group. They used a dose of rapamycin 0.1 or 0.5 mg/kg of body weight, which was given in food for 2 months. The also used a group of standard lab Wistar rats as another control. [Wistar rats do not develop AMD]. All rats were examined prior to treatment at 1.5 months of age and at 3.5 months of age by ophthalmoscopic exam.



Results

             Stages of Retinopathy in 3.5 month-old rats with and w/o rapamycin treatment

                                                             Control                  0.1 Rapa              0.5 Rapa

Stage 0                                                 4%                           10%                        27%

Stage 1                                                42%                          73%                       73%

Stage 2                                                54%                          17%                        0%


Diagnosis was based upon ophthalmoscopic examination. Prior to treatment at 1.5 months there was no difference and 20% of rats had stage 1 retinopathy.

At 3.5 months , 54% of Control, 17% of 0.1 Rapa and 0 % of 0.5 Rapa had stage 2 retinopathy. 

"In a dose-dependent manner, rapamycin decreased the incidence and severity of retinopathy."


Histological examination showed rapamycin prevents neurodegeneration. 


Rapamycin was shown by immunoblot to decrease phosphorylation of S6, the downstream target of mTOR1.



Discussion

"Herein, we demonstrated that rapamycin prevented AMD-like retinopathy in OXYS rats. More important, rapamycin suppressed disease progression, even through it was started after some rats had already developed stage 1 retinopathy."


"Taken together with other preclinical data, our work suggests rapamycin for the treatment and prevention of AMD retinopathy. In fact, preliminary data suggests that rapamycin given systemically (oral instead of intravitreal injection) can alter the clinical course of the wet form of AMD."

Abstract

"Herein, we investigated the effect of rapamycin on spontaneous retinopathy in senescence-accelerated OXYS rats, an animal model of age-related macular degeneration. Rats were treated with either 0.1 or 0.5 mg/kg rapamycin, which was given orally as a food mixture. In a dose-dependent manner, rapamycin decreased the incidence and severity of retinopathy. Rapamycin prevented destruction of ganglionar neurons in the retina...Taken together our data suggests the therapeutic potential of rapamycin for treatment and prevention of retinopathy."

Comment

This study suggests that a low dose intermittent rapamycin sufficient to decrease activity of mTOR1 may prevent AMD and blindness.


  • Privacy Policy
  • Terms and Conditions

Powered by GoDaddy