The generation of pluripotent stem cells from an individual patient would enable the large-scale production of the cell types affected by that patient's disease. These cells could in turn be used for disease modeling, drug discovery, and eventually autologous cell replacement therapies. Although recent studies have demonstrated the reprogramming of human fibroblasts to a pluripotent state, it remains unclear whether these induced pluripotent stem (iPS) cells can be produced directly from elderly patients with chronic disease. We have generated iPS cells from an 82-year-old woman diagnosed with a familial form of amyotrophic lateral sclerosis (ALS). These patient-specific iPS cells possess properties of embryonic stem cells and were successfully directed to differentiate into motor neurons, the cell type destroyed in ALS.

A four-dose course of rituximab partially preserved beta-cell function over a period of 1 year in patients with type 1 diabetes. The finding that B lymphocytes contribute to the pathogenesis of type 1 diabetes may open a new pathway for exploration in the treatment of patients with this condition. (ClinicalTrials.gov number, NCT00279305.)

Background The immunopathogenesis of type 1 diabetes mellitus (T1DM) is associated with T-lymphocyte autoimmunity. To be fully active, immune T-lymphocytes require a co-stimulatory signal in addition to the main antigen driven signal. Abatacept modulates co-stimulation andprevents full T-lymphocyte activation. We evaluated the effect of abatacept in recent-onset T1DM. Methods In this multicentre, double-masked, randomised controlled trial, 112 subjects (ages 6–36) recently diagnosed with T1DM; 77 received abatacept (10 mg/kg, maximum 1000 mg/dose) and 35 received placebo infusions intravenously on days 1, 14, 28, and monthly for a total of 27 infusions over two years. Primary outcome was baseline-adjusted geometric mean 2-hour area under the curve (AUC) serum C-peptide following a mixed meal tolerance test at two years. Secondary outcomes include difference between groups in incidence of loss of peak C-peptide to < 0·2 pmol/ml, slope of C-peptide over time, changes in HbA1c and insulin dose, and safety. This trial is registered in ClinicalTrials.gov (NCT00505375). Findings Adjusted C-peptide AUC was 59% (95% CI: 6·1%, 112%) higher at two years with abatacept (0·378 pmol/ml) versus placebo (0·238 pmol/ml) (p=0·0029). The difference between groups was present throughout the trial, with an estimated 9·6 months’ delay in decline with abatacept. There was lower HbA1c (p<0·002) but similar insulin use. There were few, clinically not significant infusion related adverse events and minimal overall adverse events. There was no increase in infections or neutropenia. Interpretation Co-stimulation modulation with abatacept slowed decline of beta cell function over two years. The beneficial effect suggests that T-lymphocyte activation still occurs around the time of clinical diagnosis of T1DM. Yet, despite continued administration of abatacept over 24 months, the decline in beta cell function with abatacept was parallel to that with placebo after six months of treatment, causing us to speculate that T-lymphocyte activation may lessen with time. Further observation will determine whether the beneficial effect continues after cessation of abatacept infusions. Funding National Institutes of Health.

Type 1 diabetes (T1D) is the result of an autoimmune destruction of pancreatic ␤ cells. The cellular and molecular defects that cause the disease remain unknown. Pluripotent cells generated from patients with T1D would be useful for disease modeling. We show here that induced pluripotent stem (iPS) cells can be generated from patients with T1D by reprogramming their adult fibroblasts with three transcription factors (OCT4, SOX2, KLF4). T1D-specific iPS cells, termed DiPS cells, have the hallmarks of pluripotency and can be differentiated into insulin-producing cells. These results are a step toward using DiPS cells in T1D disease modeling, as well as for cell replacement therapy.

Telemedicine case management improved glycemic control, blood pressure levels, and total and LDL cholesterol levels at one year of follow-up.