Abstract: The present invention relates to a method of treating PIK3CA-Related Overgrowth Spectrum (PROS) more particularly, Congenital, Lipomatous, Overgrowth, Vascular Malformations, Epidermal Nevi and Spinal/Skeletal Anomalies and/or Scoliosis (CLOVES) syndrome. To date, there are no specific treatments for patients and no animal models of PROS to better understand the physiopathology of the disorder. Inventors developed a genetic mouse model of PROS that recapitulates the human disease and demonstrated the efficacy of BYL719. Based on these results they treated two patients, one adult and one child, with severe CLOVES syndrome using BYL719. The drug had a robust efficiency on disease in the two patients inducing quick recovery of all affected organs. Thus, the invention relates to a method of treating PROS in a subject in need thereof comprising the step of administrating the subject with a therapeutically effective amount of BYL719.

Abstract: The present invention relates to a method of treating PIK3CA-Related Overgrowth Spectrum (PROS) more particularly, Congenital, Lipomatous, Overgrowth, Vascular Malformations, Epidermal Nevi and Spinal/Skeletal Anomalies and/or Scoliosis (CLOVES) 10 syndrome. To date, there are no specific treatments for patients and no animal models of PROS to better understand the physiopathology of the disorder. Inventors developed a genetic mouse model of PROS that recapitulates the human disease and demonstrated the efficacy of BYL719. Based on these results they treated two patients, one adult and one child, with severe CLOVES syndrome using BYL719. The drug had a robust efficiency on disease in the 15 two patients inducing quick recovery of all affected organs. Thus, the invention relates to a method of treating PROS in a subject in need thereof comprising the step of administrating the subject with a therapeutically effective amount of BYL719.

Abstract: The invention relates to a PI3K inhibitor for use in the treatment of keloid, hypertrophic, bum scars and/or hyperpigmentation disorders in a subject in need thereof. 19 patients underwent multiple surgeries before receiving BYL719. These surgery procedures led to a certain number of severe hypertrophic and keloid scars. Inventors observed that during treatment with oral BYL719, the length, the area and the thickness of the different scars were dramatically reducing without additional treatment. Furthermore, they observed a spontaneous that the nevi were spontaneously decolorating with BYL719. Nevus color was evaluated using an arbitrary visual scale ranging from (5: dark color to 1: normal skin color). This new approach with either BYL719 alone or in combination with other therapeutics seem to be very promising in patients with keloid, hypertrophic, and/or burn scars.

Abstract: The invention relates to a PI3K inhibitor for use in the treatment of neurofibromatosis type 1 and type 2 in a subject in need thereof. Currently there are no treatment of neurofibromatosis type 1 and 2. Patients mainly received supportive care to treat severe symptoms including surgery to remove tumors compressing nearby tissue or damaging organs, stereotactic radiosurgery or cochlear implants. Inventors have worked on immortalized NF1?/? cells and shown that PIK3CA pharmacological inhibition (BYL719) was associated with increased apoptosis as assessed by PARP cleavage in a dose dependent manner. They also decided to expose NF1?/? cells to a multitargeted therapy including BYL719+selumetinib or BYL719+selumetinib+IPA-3. Importantly, they found that both combinations led to severe apoptosis with double strand DNA break as assessed by the phosphorylation of H2aX. This new approach with either BYL719 alone or in combination with other therapeutics seem to be very promising in patients with neurofibromatosis.

Abstract: The invention relates to a method for treating mitochondrial genetic diseases. The inventors have worked with primary fibroblasts from patients and control individuals and collected protein lysates for western blotting. Importantly, they observed that the genetic mitochondrial disorders, show a significant increase in phosphorylation of ribosomal protein S6 (pS6) compared to control fibroblasts, indicative of hyperactivated mTOR signaling. Patients with mitochondrial disorders and controls cells were treated for 48 hours with DMSO or BYL719. All lines from patients with mitochondrial diseases show reduced membrane potential, determined by TMRE staining intensity, and abnormal morphology, fragmentation and the presence of depolarized (low TMRE staining) mitochondria. Treatment with BYL719 attenuated these phenotypes in all MELAS fibroblasts while having no overt impact on the control cells.

Abstract: The present invention relates to a method of treating PIK3CA-Related Overgrowth Spectrum (PROS) more particularly, Congenital, Lipomatous, Overgrowth, Vascular Malformations, Epidermal Nevi and Spinal/Skeletal Anomalies and/or Scoliosis (CLOVES) 10 syndrome. To date, there are no specific treatments for patients and no animal models of PROS to better understand the physiopathology of the disorder. Inventors developed a genetic mouse model of PROS that recapitulates the human disease and demonstrated the efficacy of BYL719. Based on these results they treated two patients, one adult and one child, with severe CLOVES syndrome using BYL719. The drug had a robust efficiency on disease in the 15 two patients inducing quick recovery of all affected organs. Thus, the invention relates to a method of treating PROS in a subject in need thereof comprising the step of administrating the subject with a therapeutically effective amount of BYL719.

Abstract: The invention relates to the diagnosis of HIV-associated nephropathy (HIVAN) based on determining the expression level of HIV nucleic acids (HIV RNA and/or DNA) in combination with the renal function of a patient. The invention also relates to a method for distinguishing between HIVAN and non-HIVAN kidney disease in a patient based on the expression level of urinary HIV nucleic acids.

Abstract: The present invention relates to the prevention or treatment of antiphospholipid syndrome (APS) in a patient in need thereof (e.g. patients affected with primary APS, a secondary APS, a catastrophic APS (CAPS) or a transplant recipient with antiphospholipid antibodies (APA)). The present invention also relates to the prevention APS-related vascular lesions in said a patient in need thereof. The present invention further relates to PI3K-AKT-mTOR pathway inhibitor for use in inhibiting endothelial m TORC activation triggered by APA in a patient in need thereof.

Abstract: The present invention is directed to the use of marker for Akt2 activation in podocytes as a biomarker to predict toxicity of mTOR inhibitors. Another aspect of the invention relates to a method for preventing graft rejection comprising administering a selective mTORC1 or Akt1 inhibitor in a subject in need thereof.