scispace - formally typeset
Search or ask a question
Author

Sudhish Mishra

Bio: Sudhish Mishra is an academic researcher from Sanjay Gandhi Post Graduate Institute of Medical Sciences. The author has contributed to research in topics: Duchenne muscular dystrophy & Muscular dystrophy. The author has an hindex of 1, co-authored 1 publications receiving 40 citations.

Papers
More filters
Journal ArticleDOI
TL;DR: DNA samples from 121 unrelated DMD/BMD patients from North India were analyzed for deletional studies with multiplex PCR and Southern hybridization, and a total of 88 patients showed intragenic deletions in the dystrophin gene.
Abstract: Population-based variations in frequency and distribution of dystrophin gene deletions have been recognized in Duchenne/Becker (DMD/BMD) muscular dystrophy patients. In the present study, DNA samples from 121 unrelated DMD/BMD patients from North India were analyzed for deletional studies with multiplex PCR and Southern hybridization. A total of 88 (73%) patients showed intragenic deletions in the dystrophin gene. The observed proportion of gene deletions is relatively high, particularly compared with that of Asian counterparts. However, the distribution of breakpoints across the gene does not show significant variations.

41 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: In this paper, a reading frame correction therapy aimed at the antisense-induced skipping of targeted exons from the premRNA was developed, which can restore the reading frame in over 75% of the patients reported in the Leiden DMD mutation database.
Abstract: The dystrophin deficiency leading to the severely progressing muscle degeneration in Duchenne muscular dystrophy (DMD) patients is caused by frame-shifting mutations in the DMD gene. We are developing a reading frame correction therapy aimed at the antisense-induced skipping of targeted exons from the premRNA. Despite introducing a (larger) deletion, an in-frame transcript is generated that allows the synthesis of a slightly shorter, but largely functional dystrophin as found in the mostly milder Becker muscular dystrophy (BMD). We have recently demonstrated both the efficacy and high efficiency of the antisense-induced skipping of numerous exons from the DMD transcript in control muscle cells. In principle, this would restore the reading frame in over 75% of the patients reported in the Leiden DMD mutation database. In this study, we in fact demonstrate the broad therapeutic applicability of this strategy in cultured muscle cells from six DMD patients carrying different deletions and a nonsense mutation. In each case, the specific skipping of the targeted exon was induced, restoring dystrophin synthesis in over 75% of cells. The protein was detectable as soon as 16 h post-transfection, then increased to significant levels at the membrane within 2 days, and was maintained for at least a week. Finally, its proper function was further suggested by the restored membranal expression of four associated proteins from the dystrophin–glycoprotein complex. These results document important progress towards a clinically applicable, small-molecule based therapy.

294 citations

Journal ArticleDOI
TL;DR: Proton NMR spectroscopic investigations on the lipid extract of the serum of Duchenne muscular dystrophy patients and healthy subjects in the northern Indian population may provide the possibility of the diagnostic importance for DMD, especially in cases where genetic analysis fails to provide the diagnosis.
Abstract: Proton NMR spectroscopic investigations on the lipid extract of the serum of 41 Duchenne muscular dystrophy (DMD) (age, mean +/- SD; 8.0 +/- 3.0 years) patients and 22 healthy subjects (age, mean +/- SD; 9.0 +/- 4.0 years) were performed in the northern Indian population. The concentration of triglycerides, phospholipids, free cholesterol, cholesterol esters and total cholesterol was significantly higher in DMD patients as compared to healthy subjects. Ratio of free-cholesterol to cholesterol-esters was also significantly higher in DMD patients. Among the individual lipids, concentration of phospholipids was found to be consistently higher in DMD patients compared to healthy subjects, with a discriminatory index of 87.5%. The highest discriminatory index of 92% was found along with the ratio of PL (phospholipids) to CHOL (cholesterol), i.e. PL/CHOL. No significant quantitative difference was observed in the serum lipid constituents of positive and negative gene deletion cases of DMD. The inferences drawn from this study may provide the possibility of the diagnostic importance for DMD, especially in cases where genetic analysis fails to provide the diagnosis.

63 citations

Journal ArticleDOI
TL;DR: An open controlled trial of 0.75 mg/Kg/day prednisolone was conducted at a stage when the patients had started falling several times in a day and stopped on their attaining a chair bound stage, thus minimising the total period of steroid therapy.
Abstract: An open controlled trial of 0.75 mg/Kg/day prednisolone was conducted at a stage when the patients had started falling several times in a day and stopped on their attaining a chair bound stage, thus minimising the total period of steroid therapy. Out of the 67 DMD patients enrolled in this study, 44 were put on prednisolone therapy and 23 served as controls. All patients were followed-up at two-monthly intervals for two years and thereafter they continued to take their respective medications till their chair-bound stage; then the drug was gradually withdrawn. In the treatment group 24 patients could not continue the trial because of adverse effects – 14 due to excessive obesity, 3 due to measles, 4 due to pulmonary tuberculosis, 2 due to recurrent throat and chest infection and 1 due to an unexplained high leukocyte count. Of the remaining 20 patients in the treatment group, steroid therapy was stopped in 5 patients as there was no improvement in power in six months. Fifteen patients in the treatment group and 19 patients in the control group could be followed regularly for 2 years and then up to chair-bound stage. Outcome parameters included fall frequency, peak expiratory flow rate, limb muscle power, ability to lift weights, time taken in getting up from squatting position, walking 9 metres and climbing 13 stairs. Maximum improvement was noted between 2 and 4 months while mild improvement in some parameters continued up to six months. All parameters remained stabilised for 1 year or so, after which there was slight deterioration. Deterioration at 2 years was, however, less than the natural course of events noted in control patients. Prednisolone treated patients and controls became chair bound at the mean age of 169 ± 9 and 132 ± 8 months respectively. Till the ideal stage of the disease and the type or dosage of starting steroid therapy is defined by specially designed studies, 0.75 mg/Kg/day prednisolone therapy may be started in DMD patients at the stage of frequent falls ( > 10 / day) on walking or increased get-up time ( > 10 s) as observed while testing Gowers’ sign; this improves muscle power and timing of motor performance within 2–4 months of onset of therapy in about 75% of those who tolerate this therapy, with a possible gain of approximately 3 years in terms of independent walking.

57 citations

Journal ArticleDOI
TL;DR: There are significant clinical benefits to be gained from a combined mutation detection protocol for carrier detection and it is recommended that mutation-specific carrier frequencies for the different classes of dystrophin mutations should be taken into account in genetic counselling practice.
Abstract: Background: Recent methodological advances have improved the detection rate for Dystrophin mutations, but there are no published studies that have measured the clinical utility of these protocols for carrier detection compared with conventional carrier testing by pedigree, serum creatine kinase levels and linkage analysis. Methods and Subjects: We measured the clinical utility ofa combined mutation detection protocol, involving quantitative PCR procedures followed by DNA sequence analysis, for the identification of Dystrophin mutation carriers in 2101 women at risk of being carriers from 348 mutation known Duchenne or Becker muscular dystrophy pedigrees. Results: The combined mutation detection protocol identified a mutation in 96% and 82% of index cases of DMD and BMD respectively. An additional 692 (33%) potential carriers were correctly classified by the combined mutation detection protocol compared with pedigree, CK levels and linkage analysis. Significantly lower mutation carrier rates were identified in the mothers of index cases with deletion mutations than predicted from theoretical considerations but these findings were not confirmed for duplication and DNA sequence mutations. Conclusions: There are significant clinical benefits to be gained from a combined mutation detection protocol for carrier detection. Genetic counseling practice should take into account mutation specific carrier frequencies for the different classes of Dystrophin mutations.

49 citations

Patent
28 Jan 2013
TL;DR: The current invention provides animproved oligonucleotide and its use for treating, ameliorating, preventing and/or delaying DMD or BMD as discussed by the authors...
Abstract: The current invention provides animproved oligonucleotide and its use for treating, ameliorating, preventing and/or delaying DMD or BMD.

32 citations