Rapamycin treatment
The discovery, in 2002, that TSC1 and TSC2 participate in a signaling pathway that regulates mTOR activity led scientists and physicians to the hypothesis that mTOR inhibitors would be beneficial for TSC and LAM patients. Rapamycin (also called Sirolimus), an mTOR inhibitor, had been used for over a decade as a drug to suppress the immune system after kidney transplantation. The first trials for rapamycin (Sirolimus) and analogues (Everolimus) for TSC and LAM patients started in 2005 and these drugs were found to be effective to reduce the size of Subependymal Griant Astrocytomas (SEGAS) in the brain, angiomyolipomas in the kidneys, and to improve the functional parameters of lungs. Recent studies report that rapamycin treatment improves the cognitive functions and autistic symptoms of TSC patients.
A problem is that rapamycin and rapamycin analogues do not kill tumor cells, but slow down their growth. Second, if treatment with rapamycin and analogues is terminated, kidney tumors tend to grow back and lung function declines. Third, a small percentage of patients (5-10%) does not respond to treatment or have significant adverse reactions to these drugs. Finally, that these drugs activate pro-survival molecules (e.g. AKT) and processed (e.g. autophagy), which makes these cells harder to kill.
Despite these drawbacks, rapamycin and rapamycin analogue therapy remains the main most effective drug treatment option currently available for TSC and LAM patients.
Angiomyolipoma Volume in the Patients with the Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis during the Study. Angiomyolipomas were visualized with the use of abdominal magnetic resonance imaging, and volumetric analysis was performed at baseline and at 2, 4, 6, 12, 18, and 24 months. The angiomyolipoma volume at each visit is expressed as a percentage of the baseline size. The dashed line represents 70% of the baseline value; data below the line indicate that the mean angiomyolipoma volume was reduced by 30% or more. (from Bissler et al. 2012 NEJM)
A problem is that rapamycin and rapamycin analogues do not kill tumor cells, but slow down their growth. Second, if treatment with rapamycin and analogues is terminated, kidney tumors tend to grow back and lung function declines. Third, a small percentage of patients (5-10%) does not respond to treatment or have significant adverse reactions to these drugs. Finally, that these drugs activate pro-survival molecules (e.g. AKT) and processed (e.g. autophagy), which makes these cells harder to kill.
Despite these drawbacks, rapamycin and rapamycin analogue therapy remains the main most effective drug treatment option currently available for TSC and LAM patients.
Angiomyolipoma Volume in the Patients with the Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis during the Study. Angiomyolipomas were visualized with the use of abdominal magnetic resonance imaging, and volumetric analysis was performed at baseline and at 2, 4, 6, 12, 18, and 24 months. The angiomyolipoma volume at each visit is expressed as a percentage of the baseline size. The dashed line represents 70% of the baseline value; data below the line indicate that the mean angiomyolipoma volume was reduced by 30% or more. (from Bissler et al. 2012 NEJM)
Updated 5 March 2018